Immune thrombocytopenia

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Autoantibodies and cytotoxic T cells accelerate platelet clearance, particularly in the spleen, and can suppress megakaryocyte platelet production. The platelet count may fluctuate abruptly after infection, vaccination or treatment, while clinical bleeding ranges from none to petechiae and mucosal loss. Major spontaneous haemorrhage is uncommon but becomes more likely with profound counts and patient-specific risks. A count is therefore a treatment input, not the outcome itself.

ITP is a diagnosis of exclusion made from history, examination, full count and expert film. Isolated thrombocytopenia with otherwise normal morphology is typical. Splenomegaly, lymphadenopathy, fever, weight loss, haemolysis, renal injury, coagulation abnormalities or other cytopenias should reopen the differential. Secondary ITP occurs with HIV, hepatitis C, autoimmune and lymphoid disease and some medicines. H pylori testing follows local prevalence and symptom pathways rather than indiscriminate use.

Treatment decisions combine bleeding, count, trajectory, lifestyle, comorbidity and patient preference. Observation avoids treatment toxicity in stable low-risk disease. Corticosteroids or IVIG raise counts more quickly but do not necessarily create lasting remission. Persistent or chronic ITP requires a shared choice: TPO-receptor agonists maintain production while taken; rituximab may induce a treatment-free response but impairs vaccine responses; splenectomy offers durable remission for some but carries lifelong sepsis and thrombosis risk and is usually deferred to allow spontaneous improvement and informed planning.

Key points

ITP is an acquired immune thrombocytopenia caused by increased platelet destruction and impaired production, diagnosed after excluding alternative causes of an isolated low count.
Confirm true thrombocytopenia with repeat count and film; platelet clumping, schistocytes, blasts, dysplasia and additional cytopenias argue for another pathway.
Bleeding risk relates to count, but age, previous bleeding, anticoagulants, hypertension, falls, infection and procedure plans substantially modify it.
Many adults with mild or no bleeding can be observed safely even at counts below the reference range; treatment aims for haemostasis, not normalisation.
Short-course corticosteroid is a common initial treatment when clinically indicated; avoid prolonged unplanned prednisolone exposure because toxicity accumulates quickly.
Intravenous immunoglobulin produces a faster temporary rise for significant bleeding, urgent procedure, pregnancy or need to avoid corticosteroid, but response is not durable.
Test for HIV and hepatitis C and review medicines, alcohol, autoimmune disease, lymphoproliferative disease and pregnancy where clinically relevant.
Platelet antibody tests have limited sensitivity and specificity and a negative result does not exclude ITP; routine marrow biopsy is unnecessary in a typical isolated presentation.
Thrombopoietin-receptor agonists, fostamatinib, rituximab and splenectomy offer second-line strategies with different speed, durability, infection, thrombosis and monitoring profiles.
ITP itself and some treatments increase thrombosis risk, so a low platelet count does not automatically protect against venous or arterial events.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Primary immune dysregulation

Platelet-directed humoral and cellular immunity develops without an identified underlying disorder, often after an immune stimulus but not caused by ordinary physical activity.

Secondary immune thrombocytopenia

HIV, hepatitis C, systemic autoimmune disease, lymphoid malignancy and selected medicines can generate an ITP phenotype requiring treatment of both trigger and bleeding risk.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Accelerated platelet clearance
Antibody-coated platelets bind Fc receptors on splenic and hepatic macrophages and are removed more rapidly from the circulation.
2
Impaired platelet production
Antibodies and T-cell effects also damage megakaryocytes, so compensatory marrow output may not fully replace peripheral destruction.
3
Variable haemostatic reserve
Young larger platelets may retain function, while vascular integrity, medicines and comorbidity determine why similar counts produce very different bleeding phenotypes.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Isolated count fall

Thrombocytopenia occurs with normal haemoglobin, white cells and film except for occasional large platelets and no systemic consumption pattern.

Platelet-type bleeding

Petechiae, easy bruising, epistaxis, gum bleeding and heavy menstruation predominate over spontaneous deep-muscle haemorrhage.

Atypical finding

Splenomegaly, nodes, fragments, anaemia, neutropenia or abnormal coagulation should prevent premature primary ITP diagnosis.

Intracranial warningRed flag

Severe headache, vomiting, focal neurology, seizure or reduced consciousness with profound thrombocytopenia needs immediate imaging and rescue therapy.

Thrombotic coexistence

Leg swelling, chest pain or focal arterial symptoms still require thrombosis assessment despite a low platelet count.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Repeat full count and filmFirst step
Why
Confirm isolated genuine thrombocytopenia and exclude fragments or blasts.
Interpretation and limitations
Clumps indicate artefact; schistocytes, dysplasia or additional cytopenias require another diagnostic pathway rather than a trial of steroids.
02
HIV and hepatitis C tests
Why
Identify treatable secondary immune causes.
Interpretation and limitations
Positive results change infection, transmission and ITP management and require consent and appropriate specialist linkage.
03
Liver, renal and haemolysis profile
Why
Exclude sequestration, organ TMA and haemolysis.
Interpretation and limitations
Liver dysfunction and splenomegaly support portal mechanisms; renal injury and haemolysis with fragments raise TMA.
04
Coagulation and fibrinogen
Why
Assess DIC or another consumptive coagulopathy when systemic illness is present.
Interpretation and limitations
Routine tests are generally normal in isolated ITP; consumption patterns redirect treatment toward the underlying critical illness.
05
Pregnancy test
Why
Identify obstetric context and treatment constraints.
Interpretation and limitations
Gestational thrombocytopenia, ITP, pre-eclampsia, HELLP and pregnancy-associated TMA are distinguished by count, timing, blood pressure, haemolysis and organs.
06
Bone-marrow examination
Why
Investigate atypical or treatment-refractory disease.
Interpretation and limitations
Not routine for a typical isolated presentation; use when other lines, morphology, systemic features or planned treatment makes marrow information consequential.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Pseudothrombocytopenia

EDTA-dependent clumping produces a low analyser count without true circulating deficiency and is resolved by film and alternative-anticoagulant sampling.

Thrombotic microangiopathy

Schistocytes, haemolytic anaemia and neurological or renal injury indicate TTP or HUS, where treating as uncomplicated ITP dangerously delays plasma exchange or complement care.

Drug-induced thrombocytopenia

A sudden severe fall after a new medicine may be immune mediated; heparin exposure with thrombosis requires the distinct HIT pathway.

Marrow failure or infiltration

Anaemia, neutropenia, blasts, dysplasia or systemic malignancy features suggest impaired production and usually require marrow and clonal investigation.

Liver disease and DIC

Splenic sequestration in portal hypertension and systemic coagulation consumption produce broader clinical, liver and coagulation abnormalities than primary isolated ITP.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01DiagnosisEstablish isolated immune thrombocytopeniaFirst stepTrue thrombocytopenia is found without immediate major bleeding.

1Review film, previous counts, medicines, alcohol, infection, vaccines, pregnancy, autoimmune symptoms, lymph nodes and spleen and assess bleeding systematically.
2Exclude pseudothrombocytopenia, TMA, DIC, liver disease, marrow failure, HIV, hepatitis C and drug or heparin causes from the phenotype.
3Name ITP only after the pattern is coherent and agree observation or treatment from bleeding, count, trajectory, comorbidity and patient priorities.

02Critical bleedRaise haemostasis on multiple frontsIntracranial, pulmonary, haemodynamically important or uncontrolled bleeding occurs.

1Resuscitate, image the bleeding site where appropriate and involve haematology, transfusion, critical care and the relevant procedural team immediately.
2Give high-dose corticosteroid and intravenous immunoglobulin through the emergency protocol, adding platelet transfusion for life-threatening bleeding after immune treatment begins.
3Control local bleeding, stop reversible antithrombotic exposure and repeat clinical, haemoglobin and platelet assessment rather than waiting for complete count normalisation.

03Persistent diseaseChoose a durable strategy by trade-offITP relapses, becomes corticosteroid dependent or remains clinically significant.

1Avoid repeated prolonged steroid courses and reassess diagnosis, adherence, secondary cause, bleeding burden, thrombosis and treatment goals.
2Compare TPO-receptor agonist, fostamatinib, rituximab and splenectomy by expected response, ongoing treatment, pregnancy, infection, thrombosis and monitoring.
3If splenectomy is chosen, complete vaccines and antimicrobial and thrombosis planning and preserve lifelong fever education and patient-held alerts.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Produces a relatively rapid immune platelet response when treatment is indicated and limits exposure to a defined short course.

Dexamethasone

A common adult initial regimen is 40 mg orally once daily for 4 days, sometimes repeated under haematology guidance; use a lower or alternative plan when toxicity risk dictates.

Hyperglycaemia, insomnia, psychosis, hypertension, infection, gastrointestinal and bone effects require anticipatory management; response may relapse and prolonged unsupervised courses are avoided.

Reduces Fc-mediated platelet clearance in significant bleeding, urgent procedures, pregnancy or selected steroid-intolerant situations.

Intravenous immunoglobulin

Haematology commonly uses 1 g/kg intravenously for one or two days, or an equivalent divided regimen, when a rapid temporary platelet rise is needed.

Headache, aseptic meningitis, haemolysis, thrombosis, fluid load and renal injury occur; use ideal or adjusted weight and infusion precautions under local policy.

Stimulates megakaryocyte platelet production in persistent or chronic ITP when an ongoing second-line strategy is appropriate.

Eltrombopag

A specialist starts and titrates the licensed once-daily oral dose to maintain a haemostatic, not normal, count, separating it from calcium, iron and other polyvalent cations.

Monitor liver tests, thrombosis, marrow reticulin and excessive counts; food and cation interactions reduce absorption and treatment effect wanes after cessation.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Critical haemorrhage

Intracranial, gastrointestinal, pulmonary or uncontrolled gynaecological bleeding can cause rapid neurological, haemodynamic or respiratory compromise requiring combined immune and component therapy.

Treatment toxicity

Corticosteroids cause infection, hyperglycaemia, mood change and bone injury, while prolonged immune therapy creates cumulative adverse effects that may exceed bleeding risk.

Thrombosis

ITP, inflammation, TPO-receptor agonists, splenectomy and conventional vascular risks can combine to produce venous or arterial thrombosis despite thrombocytopenia.

Post-splenectomy infection

Loss of splenic immune function creates lifelong risk from encapsulated organisms, requiring vaccination, prophylaxis, patient-held alerts and immediate fever treatment.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Track bleeding score, menstrual loss, haemoglobin and function alongside count; a laboratory rise without clinical benefit may not justify toxicity.
During corticosteroid therapy review glucose, blood pressure, sleep, mood, infection, gastric and bone risk and enforce the planned stop date.
For TPO-receptor agonists measure counts frequently during titration and after changes, then monitor liver or product-specific safety and thrombosis symptoms.
Reassess anticoagulant and antiplatelet need collaboratively rather than stopping essential vascular prevention indefinitely without a restart plan.
Before and after splenectomy verify vaccines, antibiotic supply, fever action, thrombosis risk and a patient-held asplenia alert.
Reopen the diagnosis after loss of response, new anaemia or neutropenia, splenomegaly, nodes, haemolysis or an abnormal film.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Treat haemostasis, not normality

A stable safe count with no clinically important bleeding is a better goal than treatment toxicity used to reach the reference range.

Large platelets are supportive

Young platelets may be enlarged during peripheral destruction, but morphology cannot replace exclusion of inherited macrothrombocytopenia and other causes.

IVIG buys time

Its rapid response is useful around bleeding or procedures, but the effect is temporary and needs a longer-term plan.

Low count does not prevent clots

Disease inflammation, splenectomy and some therapies add thrombosis risk, requiring symptom-led evaluation and balanced antithrombotic decisions.

11Common pitfallsFrequent interpretation and management errors.

01
Diagnosing ITP without reviewing the film.
02
Treating an asymptomatic count to normality automatically.
03
Using prolonged corticosteroids without a stop plan.
04
Giving platelet transfusion alone for routine non-critical ITP.
05
Assuming thrombocytopenia completely excludes dangerous thrombosis.
06
Forgetting lifelong infection prevention after splenectomy.